Newly developed molecule tested as a delivery vehicle to image and kill brain tumors

ScienceDaily (Aug. 3, 2011) — A single compound with dual function -- the ability to deliver a diagnostic and therapeutic agent -- may one day be used to enhance the diagnosis, imaging and treatment of brain tumors, according to findings from Virginia Commonwealth University and Virginia Tech.

Glioblastomas are the most common and aggressive brain tumor in humans, with a high rate of relapse. These tumor cells often extend beyond the well-defined tumor margins making it extremely difficult for clinicians and radiologists to visualize with current imaging techniques. Researchers have been investigating enhanced methods of attacking these cells in order to possibly delay or prevent brain tumor relapse.

In a study published in the August issue of the journal Radiology, the research team led by Panos Fatouros, Ph.D., a former professor and chair of the Division of Radiation Physics and Biology in the VCU School of Medicine who retired in 2010, demonstrated that a nanoparticle containing an MRI diagnostic agent can effectively be imaged within the brain tumor and provide radiation therapy in an animal model.

The nanoparticle filled with gadolinium, a sensitive MRI contrast agent for imaging, and coupled with radioactive lutetium 177 to deliver brachytherapy, is known as a theranostic agent -- a single compound capable of delivering simultaneously effective treatment and imaging. The lutetium 177 is attached to the outside of the carbon cage of the nanoparticle.

"We believe the clustering properties of this nanoplatform prolong its retention within the tumor, thereby allowing a higher radiation dose to be delivered locally," said Michael Shultz, Ph.D., a research fellow in Fatouros' lab in the Department of Radiology in the VCU School of Medicine.

"This theranostic agent could potentially provide critical data about tumor response to therapy by means of longitudinal imaging without further contrast administration," said Fatouros.

A nanoparticle called a functionalized metallofullerene (fMF), also known as a "buckyball," served as the basis of this work and was created by study collaborator, Harry Dorn, Ph.D., a chemistry professor at Virginia Tech, and his team. In 1999, Dorn and his colleagues were able to encapsulate rare earth metals in the hollow interior of these nanoparticles that can easily be recognized by MRI techniques.

"Although this is a limited animal study, it shows great promise and hopefully this metallofullerene platform will be extended to humans," said Dorn.

Fatouros, who is the corresponding author on the study, Shultz and Dorn collaborated with John D. Wilson, Ph.D., associate professor in the VCU Department of Radiology; Christine E. Fuller, M.D., professor and director of neuropathology and autopsy pathology at VCU; and Jianyuan "Jason" Zhang, a graduate student in chemistry at Virginia Tech from Beijing, China.

The study was funded by grants to Fatouros from the National Institutes of Health's National Cancer Institute, and to Dorn from the National Science Foundation.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Virginia Commonwealth University.

Journal Reference:

John D. Wilson, Christine E. Fuller, Jianyuan Zhang, Harry C. Dorn, Panos P. Fatouros. Metallofullerene-based Nanoplatform for Brain Tumor Brachytherapy and Longitudinal Imaging in a Murine Orthotopic Xenograft Model. Radiology, 2011; DOI: 10.1148/radiol.11102569

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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E-cigarette or drug delivery device? Questions about safety, usage and future implications of new nicotine delivery products

ScienceDaily (July 21, 2011) — Devices marketed as "electronic cigarettes" are in reality crude drug delivery systems for refined nicotine, posing unknown risks with little new benefits to smokers, according to tobacco control experts.

In a "Perspective" published in the New England Journal of Medicine, researchers from the Legacy's Steven A. Schroeder National Institute for Tobacco Research and Policy Studies explore the current regulatory climate around electronic cigarettes ("e-cigarettes") and their safety. The authors, Nathan K. Cobb, MD, a pulmonologist and assistant professor at Georgetown University Medical Center, and David B. Abrams, PhD, executive director of the Schroeder Institute, also question future implications for physicians, policy makers and e-cigarette users.

E-cigarettes are constructed to mimic real cigarettes in size and appearance, but contain no tobacco and are not cigarettes at all. In reality they are delivery devices for refined nicotine, having more in common with inhalers used to treat asthma or other delivery devices for both approved and illicit drugs. Though individual brands vary in construction, the products generally produce a propylene glycol mist containing nicotine along with flavorings and other chemicals.

Currently, three interrelated products are being sold: the delivery device itself; cartridges that can contain up to 20 mg of nicotine; and refill kits that allow consumers to fill used cartridges with replacement nicotine solution. Some refill bottles, easily obtained over the Internet, contain enough nicotine to kill an adult if accidentally ingested.

The U.S. Food and Drug Administration (FDA) announced April 25, 2011, that it would regulate e-cigarettes as "tobacco products" and not as "drug-delivery devices." That action came after federal courts blocked the agency from regulating the products as drug-delivery devices. The courts maintained that, under the 2009 Family Smoking Prevention and Tobacco Control Act (FSPTCA), the FDA must regulate as tobacco products any product that contains nicotine from tobacco and that makes no claims to be therapeutic. These decisions together, the authors note, "upend[ed] the status quo" by having the effect of allowing the sale of unregulated refined nicotine directly to consumers, unless and until the FDA takes further action.

"The court's decision that e-cigarettes should be regulated as tobacco products and not as drug-delivery devices has substantially delayed the FDA regulatory process that normally protects the public health. It has the practical effect of allowing manufacturers to sell potentially dangerous refined nicotine products directly to consumers," said Cobb. "It is entirely possible that future modifications to the products will improve the efficiency of nicotine delivery and could dramatically increase the risks of addiction, abuse and serious overdose."

While most devices and nicotine fluids are produced by small manufacturers, Cobb and Abrams note that the fact that leading cigarette manufacturers Philip Morris International and British American Tobacco recently purchased sophisticated nicotine inhaler technologies may be an indication that both companies are developing next generation nicotine delivery devices of their own.

Abrams, a professor at Johns Hopkins Bloomberg School of Public Health added "Any refined nicotine product, whether used for smoking cessation and tested and approved by the FDA (like the Nicotrol inhaler) or a new product designed for 'reduced or modified' risk, can and must be tested and strictly regulated before being introduced to the market."

The authors argue that a comprehensive approach to regulating products containing refined nicotine is needed to protect the public's health and should involve Congress, the courts and the FDA.

In this piece, Cobb and Abrams discuss several safety concerns:

Testing of cartridges reveals poor quality control, variability in nicotine content among brands, and deviations between label claims and cartridge content.The devices do not reliably deliver nicotine, and have not been sufficiently evaluated in scientific studies the way the FDA requires of other drugs and devices used for smoking cessation. Smokers attempting to use e-cigarettes as quitting aids will most likely find them ineffective due to the fluctuating nicotine content and unpredictable delivery.Manufacturers sell cartridges with a range of up to 20 milligrams of nicotine. However, refill kits allow consumers to fill used cartridges with replacement solutions at much higher doses. In fact, the devices are not limited to delivering nicotine. The paper notes that instructions for filling cartridges with marijuana hash oil can be easily accessed on the Internet.The safety of inhaling propylene glycol over an extended period of time has not been studied in humans.E-cigarettes may serve as a "bridge product" that smokers use in places where traditional tobacco smoking is prohibited, thus perpetuating their addiction and use of real cigarettes. Additionally, they may be used as a 'starter' product for young people considering smoking, especially since the cartridges can be purchased over the Internet with tempting flavoring like grape and chocolate.

In their conclusion, Cobb and Abrams counter the argument made by e-cigarette advocates that taking the devices off the market could mean current users would be forced to return to traditional tobacco products. Instead, the two researchers point to the multiple pharmaceutical-grade nicotine products on the market that have been regulated, approved and deemed safe and effective by the FDA, including patches, gums, lozenges, nasal sprays and even an FDA-approved inhaler. The two researchers also state that current users should pursue research-proven effective cessation tools, such as nicotine replacement products, telephone quit lines, and Web-based cessation services, as well as non-nicotine pharmacotherapies like bupropion and varenicline.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Georgetown University Medical Center, via EurekAlert!, a service of AAAS.

Journal Reference:

Nathan K. Cobb, David B. Abrams. E-Cigarette or Drug-Delivery Device? Regulating Novel Nicotine Products. New England Journal of Medicine, 2011; 365 (3): 193 DOI: 10.1056/NEJMp1105249

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Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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